The proposed research will investigate the anatomical and cellular substrates mediating behavioral sensitization to the daily administration of two drugs of abuse, cocaine and morphine. The search for the site of action and neuronal correlates of the enduring behavioral changes that occur in the brain as a result of chronic cocaine or morphine administration constitutes my major career goal. The ultimate progression of which is to develop biological interventions to assist in alleviating the behavioral problems associated with long term drug abuse in humans. Within this context, the immediate goal is to evaluate the role of the A10 dopamine neurons in behavioral sensitization, using in vivo neurochemical measures of dopamine and GABA release. Also, the density of dopamine, GABA and opioid receptors, and the levels of mRNA for some proteins relevant to dopamine and GABA neurotransmission will be measured with light microscopic autoradiography in behaviorally sensitized rats. In addition, a role for GTP binding proteins and K+ conductance will be determined.